Introduction In patients with chronic obstructive pulmonary disease (COPD), statins may improve lung function and reduce exacerbations. In COPD, growth differentiation factor-15 (GDF-15) has been shown to correlate with increasing age, current smoking, and greater comorbidity, and to predict disease outcomes; however, the effect of statins on GDF-15 is not known. Material and methods This study was designed as a post-hoc analysis of GDF-15 levels in serum samples obtained from 54 patients with COPD (49 men; 90.7%), who had a 1-second forced expiratory volume (FEV1) to forced vital capacity (FVC) ratio < 0.7. Patients assigned (1 : 1) to receive simvastatin (40 mg/day) or to remain without such treatment were followed for 3 months. Lung function and laboratory parameters, including C-reactive protein, tumor necrosis factor-a (TNF-a), interleukin-6, and plasminogen activator inhibitor type 1 (PAI-1), were also assessed. Results Baseline GDF-15 concentrations (median: 907.5 pg/ml, interquartile range: 720–1095 pg/ml) correlated negatively with FEV1 (r = –0.38, p < 0.01) and positively with age (r = 0.32, p = 0.017), TNF-a (r = 0.31, p = 0.031), and PAI-1 (r = 0.40, p < 0.01), but not with lipid profile or other variables. Simvastatin reduced GDF-15 by 23% at 3 months compared to baseline (p < 0.01), independently of changes in lipid variables or inflammatory markers. At both 1 and 3 months, GDF-15 levels in the statin-treated group were 14% and 22% lower compared to the untreated control group (both p < 0.05). Conclusions Our study suggests that statin treatment can reduce circulating GDF-15 levels associated with COPD severity, which may be an additional benefit of such treatment beyond lipid-lowering or anti-inflammatory effects.

Introduction Immunoglobulin A nephropathy (IgAN), membranous nephropathy (MN), and diabetic nephropathy (DN) are prominent contributors to chronic kidney disease burden. Our main objective was to contribute to understanding of metabolic profiles of these three major types of nephropathies and identify potential metabolic biomarkers. Material and methods Kidney samples of 20 sex- and age-matched patients with biopsy-proven IgAN, MN, DN, and controls without any kidney diseases were included. Ultra high performance liquid chromatography-mass spectrometry analysis was conducted. t-test was used to calculate statistical significance of the identified metabolites. Metabolic pathways were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Specificity, sensitivity and area under the curve (AUC) were calculated to evaluate the predictive performance of metabolites. Results Among 557 identified differential metabolites, only 118 were found in all three comparison groups. Differential metabolites of IgAN vs controls were significantly enriched in arachidonic acid metabolism, starch and sucrose metabolism, ferroptosis, and other pathways. In the DN group, metabolites were mainly enriched in phenylalanine, tyrosine and tryptophan biosynthesis, histidine metabolism, etc. MN-enriched pathways included steroid hormone biosynthesis, neuroactive ligand-receptor interaction, and bile secretion. In the positive mode, cumulative AUC values for comparison pairs IgAN vs controls, MN vs controls, and DN vs controls were 0.965, 0.972, and 0.573, respectively, whereas in the negative mode the AUC values of all three pairs were slightly above 0.65. Conclusions IgAN, MN and DN have similar but distinct metabolic profiles. Only positive node metabolites of IgAN and MN exhibited great predictive performance.

Introduction The objective of this study was to evaluate the association between anthropometrically predicted visceral adipose tissue (apVAT) and mortality among individuals with non-alcoholic fatty liver disease (NAFLD). Material and methods This study analyzed 6206 NAFLD participants from the National Health and Nutrition Examination Survey. NAFLD was identified using the United States Fatty Liver Index (USFLI) or Fatty Liver Index (FLI). Baseline apVAT, an estimate of visceral fat derived from anthropometric parameters including age, body mass index (BMI), waist circumference (WC), and thigh circumference, was calculated using validated sex-specific equations. Mortality outcomes were determined by linking data to National Death Index (NDI) records up to December 31, 2019. Cox proportional hazards models and restricted cubic splines were used to examine associations, and time-dependent receiver operating characteristic (ROC) analyses were used to compare apVAT with other obesity indices including BMI, WC, thigh circumference, waist-to-height ratio (WHtR), relative fat mass (RFM), and weight-adjusted waist index (WWI). Results During a median follow-up period of 187 months, 1884 deaths from all causes and 517 from cardiovascular causes were observed. Multivariable-adjusted Cox analysis showed that the highest apVAT quartile had hazard ratios of 3.83 (3.01–4.87) for all-cause mortality and 3.47 (2.13–5.65) for cardiovascular mortality, compared to the lowest quartile. A nonlinear relationship between apVAT and mortality risk was identified. apVAT showed the highest predictive value for mortality risk compared with BMI, WC, thigh circumference, WHtR, RFM, and WWI. Conclusions Elevated apVAT levels are correlated with increased mortality risk in NAFLD, highlighting its potential as a prognostic marker.

Introduction Osteoarthritis (OA) is a common chronic joint disease that severely affects patients’ quality of life and causes a significant socioeconomic burden. The aim of this study was to investigate the association between relative fat mass (RFM) and OA and to assess the diagnostic efficacy of RFM in predicting OA risk. Material and methods We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2020. Thirty-nine thousand six hundred and fifty-eight study participants were included in the study, which used multifactorial logistic regression analyses, stratified analyses, restricted cubic spline curves (RCS), and ROC curves to explore the association between RFM and OA. Results RFM was significantly and positively associated with OA, which remained statistically significant after correction for confounders (OR = 1.062, 95% CI: 1.056–1.069, p < 0.0001). Restricted cubic spline (RCS) analysis showed a J-shaped relationship between RFM and OA (p = 0.024 for non-linear test). Stratified analyses further confirmed that the association between RFM and OA was positive in all subgroups, and the strength of this association varied by age and ethnicity (p < 0.05 for interaction). ROC curve analyses showed that RFM was significantly more diagnostic of OA than body weight, waist circumference (WC) and body mass index (BMI), with areas under the curve (AUC) of 0.646, 0.550, 0.621 and 0.550, respectively. Conclusions RFM may be an important risk factor for OA and has a diagnostic efficacy superior to traditional anthropometric indices in predicting OA risk. Future studies should further explore the mechanisms linking RFM and OA and validate its clinical applicability, with a view to providing new insights and methods for the prevention and diagnosis of OA.

Introduction The risk of secondary cancers in breast cancer survivors remains a significant concern. This study aimed to evaluate the association between treatment modalities and the time to development of secondary cancers in patients after mastectomy or breast-conserving therapy (BCT). Material and methods A retrospective analysis was conducted on 6590 patients from 2 centres (Poznan and Gorzow, Poland) treated for breast cancer between 2017 and 2022. A total of 149 patients from this group developed secondary cancer. Data included demographic and clinical characteristics, treatment types (chemotherapy, hormonotherapy, radiotherapy), and subtypes of primary breast cancer (luminal, triple negative, HER2 positive). Statistical methods included Kaplan-Meier analysis, Cox proportional hazards models, and <i>X</i><sup>2</sup> tests. Results The median time to secondary cancer detection was significantly shorter in patients with TNBC/HER2+ subtypes (2.8 years) compared to luminal subtypes (6.1 years; p = 0.024). TNBC/HER2+ subtypes were associated with a 1.9-fold increased risk of secondary cancers (HR = 1.93; p = 0.048). No significant association was found between treatment type and the occurrence of secondary cancers (p > 0.05). However, combined therapies (e.g. chemotherapy + hormonotherapy) showed a trend toward reduced risk (HR = 0.53; p = 0.061). The most common secondary cancers were gastrointestinal malignancies (27%) and gynaecological cancers (15%). Conclusions The subtype of primary breast cancer significantly influences the time to secondary cancer development, with TNBC/HER2+ patients at higher risk. Treatment modalities did not significantly affect secondary cancer risk, but combined therapies may offer protective effects. These findings highlight the need for tailored surveillance strategies based on tumour biology.

Introduction Metabolic syndrome (MetS) is a complex condition involving obesity, hyperglycemia, dyslipidemia, and hypertension. Preptin, a novel molecule co-secreted with insulin from pancreatic β-cells, has been suggested to play a role in insulin resistance and glucose and lipid metabolism. This study aimed to evaluate the differences in serum preptin levels between healthy controls and MetS patients, and to investigate its relationship with clinical parameters. Material and methods The study included forty MetS patients and forty age- and sex-matched healthy controls. Demographic and clinical data were collected, the serum preptin levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA). The relationships between the serum preptin levels and clinic parameters were assessed. Results Serum preptin levels were significantly higher in MetS patients compared to the control group (53.77 pg/mL vs. 40.77 pg/mL, p<0.001). MetS patients also had higher triglyceride, cholesterol, low-density lipoprotein cholesterol (LDL-C), fasting glucose, Hemoglobin A1c (HbA1c), insulin, and Homeostatic model assessment of insulin resistance (HOMA-IR) values compared to controls (all p<0.001). A positive correlation was found between serum preptin, insulin (r=0.432, %95 CI:0.07-0.57, p=0.0050), and HOMA-IR (r=0.426, %95 CI:0.08-0.56, p=0.0060) in the MetS group. Conclusions The results indicate that serum preptin levels are significantly elevated in MetS patients. Furthermore, high serum preptin levels were positively correlated with insulin and insulin resistance. These results suggest that preptin may be involved in the insulin resistance pathway via insulin-like growth factor II (IGF-II) modulation. Therefore, further extensive studies are required to fully understand the precise role in MetS and underlying mechanisms of preptin.

IntroductionThis study aimed to evaluate the serum levels of γ-Klotho and fibroblast growth factor 2 (FGF2) in patients with pressure ulcers.Material and methodsPatients aged ≥18 years receiving care from Home Health Services were included. The case group consisted of individuals with stage 2–4 pressure ulcers, while the control group comprised patients without ulcers, matched for age or gender. Sociodemographic characteristics, medical device usage, and nutritional status were assessed for all participants. In the case group, additional data regarding ulcer site, stage, number, and dimensions were collected. Serum levels of γ-Klotho and FGF2 were measured using the ELISA method.ResultsA total of 80 participants were enrolled (40 (50.0%) in each group). FGF2 level was 220.8 [26.8] pg/mL in the case group and 219.1 [29.1] pg/mL in the control group (p=0.577). Similarly, γ-Klotho was 1448.4 [158.6] pg/mL in the case group and 1421.3 [232.8] pg/mL in the control group (p=0.453). Conversely, a significant correlation was observed between γ-Klotho and FGF2 levels in the case group (p = 0.048), whereas no such association was found in the control group (p = 0.164). Additionally, FGF2 levels were positively associated with the number, width, and length of the wounds (p=0.003, p=0.007, and p=0.012, respectively), while a negative correlation was observed between γ-Klotho levels and wound duration (p=0.026).ConclusionsAlthough serum levels did not differ between groups, the exclusive correlation between γ-Klotho and FGF2 in the pressure ulcer group may indicate a role in chronic wound processes, warranting further investigation.

IntroductionIdentifying new drug targets is essential for improving breast cancer survival. The proteome provides a rich source for potential therapeutic targets. This study aimed to identify protein markers and therapeutic targets for breast cancer by using proteome-wide Mendelian randomization (MR).Material and methodsProtein quantitative trait loci (pQTL) data were obtained from four large-scaled proteomic studies, including 17,267 circulating protein markers. Genetic associations with breast cancer survival were derived from a large-scale GWAS meta-analysis (37,954 cases, 2,900 deaths). Proteome-wide MR was performed to assess the association between proteins and breast cancer survival, complemented by single-cell expression analysis to identify enriched cell types. Protein-protein interactions (PPI) and druggability assessments were also conducted to prioritize therapeutic targets.ResultsGene prediction levels for 27 proteins were found to be associated with breast cancer survival. Among these, eight proteins (ADAM15, CD83, SH3BGRL3, SNCG, ANXA1, GRHPR, ALDH2, and MTHFD2) showed the strongest evidence of association, while four proteins (ARG2, RPL14, NFU1, and TXNL4B) demonstrated a strong but slightly weaker correlation. Notably, SH3BGRL3, GRHPR, ARG2, RPL14, NFU1, and TXNL4B were newly identified as circulating protein markers significantly associated with breast cancer prognosis. Druggability revealed that 13 of these proteins were already targeted by existing drugs, offering potential for breast cancer treatment.ConclusionsWe identified 27 genes associated with overall and subtype-specific breast cancer survival, providing potential prognostic biomarkers and therapeutic targets, and offering new avenues for improving breast cancer management.

IntroductionThe aim of the study was to conduct a meta-analysis evaluating the efficacy of four antidepressants combined with commonly used opioid analgesics for the treatment of cancer-related neuropathic pain.Material and methodsA comprehensive search of Chinese and English databases was performed to identify relevant studies investigating the combination of duloxetine, venlafaxine, amitriptyline, or fluoxetine with opioid analgesics in managing cancer-related neuropathic pain.ResultsSeventeen studies published between 2005 and 2024, involving 1,636 patients, were included. Among them, ten were randomized controlled trials (RCTs) and seven were non-RCTs. Six studies reported opioid consumption, and meta-analysis of continuous data showed significantly lower opioid use in the treatment group compared to controls (OR = –2.99, 95% CI: –4.51 to –1.48, Z = –3.86, p < 0.01). Eleven studies assessed pain scores, with pooled results indicating significantly greater pain reduction in the treatment group (OR = –1.03, 95% CI: –1.44 to –0.62, Z = –4.94, p < 0.01). Eight studies reported depression scores, revealing significantly lower depression levels in the treatment group (OR = –2.72, 95% CI: –3.74 to –1.69, Z = –5.19, p < 0.01). Eight studies reported quality of life, and a meta-analysis of continuous variables showed no significant difference in the quality of life scores between the two groups (OR = –1.01, 95% CI: –2.30 to 0.28, Z = –1.54, p = 0.12). Eight studies reported treatment efficacy, and a meta-analysis of binary variables revealed that the treatment group had significantly higher efficacy than the control group (OR = 0.72, 95% CI: 0.29 to 1.15, Z = 3.27, p < 0.01). Five studies reported adverse reactions, with no significant difference observed between groups (OR = 0.14, 95% CI: –0.41 to 0.68, Z = 0.49, p = 0.62). Funnel plot analysis suggested publication bias in pain score outcomes, potentially due to variability in pain assessment methods and timing.ConclusionsCombining duloxetine, venlafaxine, amitriptyline, or fluoxetine with commonly used opioid analgesics effectively alleviates cancer-related neuropathic pain with minimal adverse effects. This therapeutic approach offers flexible application in clinical practice.